Expert Opinion – Professor Josef Vormoor and Dr Olaf Heidenreich

Being told your child has cancer is every parent’s worst nightmare. But every year, around 1500 families are given this devastating news. And while survival rates for childhood cancers have improved significantly, around 300 children still lose their lives to cancer each year.

That’s 300 too many and we’re determined to bring that number down to zero. To do that, we need to have the brightest and most committed minds on board. So, in April this year, we were pleased to support an application for funding from Professor Josef Vormoor and Dr Olaf Heidenreich, both at the Northern Institute for Cancer Research in Newcastle.

Josef Vormoor: It is a cancer of white blood cells called lymphocytes (also known as B-cells and T cells) which are important for defending the body against disease. Lymphocytes are made from blood stem cells in the bone marrow and ALL arises when the bone marrow starts producing too many immature lymphocytes (called lymphoblasts) which can’t function properly. The excess of abnormal cells in blood prevents the immune system from doing its job and it can also cause other problems.

Josef Vormoor: My work in the clinic. ALL is the most common form of childhood leukaemia and although we can successfully treat the vast majority of children with ALL, there are still children whose cancers do not respond so we need to have more options available for them. And our current treatments have side-effects; some of which can have consequences decades later. So we really need better treatments for all our children. Our dream is to find new targets for new drugs that specifically target leukaemia and thus have fewer side-effects.

Cancer Research UK:What aspect of ALL interests you the most?

Josef Vormoor:To keep growing, ALL needs a constant supply of leukemia cells. And this is what we’re interested in. We want to know how leukemia cells replenish themselves or “self-renew”, because once we know how it works, we might be able to interrupt it.

Cancer Research UK: Could you tell us more about self-renewal?

Olaf Heidenreich: It’s a type of cell division that is usually associated with stem cells and means that that at least one daughter cell is produced which is identical to the original cell; in other words the birth of a new stem cell. Only stem cells are capable of reproducing themselves and of forming all the other cells in a particular organ. A blood stem cell, for example, can produce all the different cells in the blood, including white cell, red cells and platelets.

In cancer, the cells that can divide indefinitely and maintain the disease are called “cancer stem cells”. Like normal stem cells, they can either self-renew, or produce daughter cells that no longer divide.

Cancer Research UK: Aren’t all cancerous cells cancer stem cells?

Josef Vormoor: Not always. In most cancer types, cancer stem cells appear to be very rare; but we’ve shown that in ALL, nearly all cancerous cells can drive the disease forward.

Cancer Research UK: How do you plan to study self-renewal in leukemic stem cells?

Olaf Heidenreich: The human genome encodes roughly 20,000 genes and we want to home in on the genes needed to keep ALL going. If a gene is important for self-renewal, turning off that gene should prevent self-renewal from happening.

Using novel technology we’re going to disable all 20,000 genes individually in ALL cells, look for cells which have lost their ability to self-renew and then study the gene we meddled with.

Cancer Research UK: What would the next step be?

Josef Vormoor: Translating this into treatments for patients. Once we’ve identified molecules that are important for self-renewal in leukaemia, we’ll need to understand how they work. Then, we can start thinking about developing new drugs if they aren’t available already. It’s a long and ambitious project but to make a real difference, we need drugs that attack the leukemic cells in a completely new way.

Cancer Research UK: How would these drugs differ from the ones we’re currently using?

Olaf Heidenreich: Most drugs try to induce the leukemic cells to die. But cancer cells can develop ways to bypass this so the drugs stop being useful. We’d like to prevent leukemic cells from maintaining and replenishing the disease. So if a leukaemia cell were a car that had lost control, current drugs try to stop it by causing a crash but we just want to remove the spark plug. These drugs would probably supplement rather than replace current drugs, but their use could allow us to reduce the dose of conventional chemotherapies and that might mean fewer side-effects for patients.

Cancer Research UK: What sort of challenges do you expect to face along the way?

Olaf Heidenreich: The real challenge will be to hit a leukemic cell without hitting healthy cells. Current treatments can harm the blood cells that help fight infection and this is why we get many of the side-effects we see. If we succeed, we’ll be able to avoid many of these problems.

Cancer Research UK: How will you ensure that healthy bone marrow stem cells won’t be affected by your treatment?

Josef Vormoor: Self-renewal in leukemic stem cells is very different to self-renewal in blood stem cells (also called hematopoietic stem cells) that live in the bone marrow. So targeting the pathways that control leukemic self-renewal should leave hematopoietic stem cells unharmed. So even if healthy B and T lymphocytes were affected by these treatments, bone marrow stem cells would be able to regenerate them.

Cancer Research UK: What drew you to Newcastle?

Josef Vormoor: I was here for a year as a medical student. I did a project with Professor Adrian Harris and that really motivated me to become a clinician scientist. It was the research environment and the clinical programme at the Great North Children’s Hospital that attracted me. Today, Newcastle is one of the leading places in Europe for childhood cancer research.

Josef Vormoor: Yes. The drug discovery programme led by Professors Herbie Newell and Roger Griffin is very strong. We have medicinal chemists here and the Experimental Cancer Medicine Centre for early-phase clinical trials. So we have all the tools to take our research forward into a clinical setting.

Cancer Research UK: What inspires you the most in your job?

Josef Vormoor: I’m often asked whether being a paediatric oncologist is depressing. It isn’t, because we can cure two thirds to eighty per cent of children. That’s incredible considering that only a generation ago, the majority of children with cancer died. But children are still dying today. So if I could find a treatment that stopped that, it would be the best thing I could do in my life. But in the end, it doesn’t matter who finds a cure – the key thing is that somebody finds it.

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